Study to Assess the Efficacy and Safety of Endolex Forte VErsus Diosmin and Hesperidin in Reducing VeNous Insufficiency (EVELINE)

A Comparative Study to Assess the Efficacy and Safety of Endolex Forte vs Diosmin and Hesperidin in Reducing the symptomatoLogy of Patients With ChronIc VeNous Insufficiency Between Functional Classes CEAP 1-4, During a Period of 6 Months

The trial is designed as a randomized, multicenter, open label, comparative, 6 months, clinical study.

Study Overview

• Status: Unknown
• Conditions: Chronic Venous Insufficiency
• Intervention / Treatment: Dietary supplement: Endolex Forte®; Dietary supplement: A combination of diosmin and hesperidin

Detailed Description

A randomized, multicentered, open label, comparative study to assess the efficacy and safety of Endolex Forte® versus a combination of micronized diosmin (450 mg) and micronized hesperidin (50 mg) in reducing the symptomatology of patients diagnosed with Chronic Venous Insufficiency which is rated between functional classes CEAP 1-4, during a period of 6 months.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dionisio Barattini, MD; Phone Number: +39 335 5437574; Email: barattini@operacro.com
• Study Contact Backup: Name: Serban Rosu, MD; Phone Number: +40 722 313224; Email: rosu@operacro.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients, male or females aged 18 to 75 years old
• BMI≤40
• Presence of chronic venous insufficiency which is rated between functional classes CEAP 1-4
• Patients diagnosed with superficial vein thrombophlebitis and have skin reaction by redness, swelling, fever and pain symptoms.or patients presenting a painful venous symptomatology in the lower limbs for at least 30 days.
• Willing and able to give written informed consent prior to participation in the trial
• Patients expected to be compliant with the study treatment

Exclusion Criteria:

• Known allergy to the product's ingredients
• Pregnancy or breastfeeding
• Patient is involved in any other clinical trial
• Deep vein thrombosis
• Stasis dermatitis
• The patient is taking non-steroids anti-inflammatory drugs include oral , topical creams or patch form)
• Open ulcers or lower extremity amputation
• Patient treated by venotonic treatments or vascular protectants or assimilated dietary supplements or homeopathic treatments or diuretics within 15 days prior inclusion
• Patient presenting permanent oedema,
• Patient with a history of lower limbs trauma responsible for sequel pains
• NYHA III and IV Heart Failure
• Renal Failure
• Untreated or uncontrolled Arterial Hypertension
• Hepatic Failure
• History of a known liver disease such as hepatitis A, hepatitis B, or C.
• Malignant neoplasms, from any etiology, or who are receiving any type of anticancer treatment, unless when properly treated and with no evidence of recurrence during the last five years
• Previous history of alcoholism, drug abuse, psychological or emotional problems in the last 5 years that can invalidate the Informed Consent Form or restrain participant's ability to comply with the requirements of the protocol.
• Immobility.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endolex Forte®; Endolex Forte® oral capsules administered from Baseline Visit until Day 180, two capsules per day.	Dietary supplement: Endolex Forte®; Endolex Forte® oral capsules administered from Baseline Visit until Day 180, two capsules per day.
Active Comparator: A combination of diosmin and hesperidin; A combination of diosmin and hesperidin is a combination of micronized diosmin (450 mg) and micronized hesperidin (50 mg) film-coated tablets administered from Baseline Visit until Day 180, two tablets per day.	Dietary supplement: A combination of diosmin and hesperidin; A combination of diosmin and hesperidin is a combination of micronized diosmin (450 mg) and micronized hesperidin (50 mg) film-coated tablets administered from Baseline Visit until Day 180, two tablets per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in limb volume determination at day 180 (water displacement method)	180 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in limb volume determination at day 90 (water displacement method)	90 days
Change from pre-treatment (baseline) in the calf circumference on treatment day 30	30 days
Change from pre-treatment (baseline) in the calf circumference on treatment day 180	180 days
Change from baseline in the subjective symptoms of CVI (tired, heavy legs, sensation of tension in the legs, pain in the legs) measured by Visual Analogue Scales (VAS) at day 90	90 days
Change from baseline in the subjective symptoms of CVI (tired, heavy legs, sensation of tension in the legs, pain in the legs) measured by Visual Analogue Scales (VAS) at day 180	180 days
Global assessment of efficacy by the investigator at day 180	180 days
Questionnaire on improvement in symptoms at day 180 (CIVIQ-20)	180 days
Global assessment of tolerability by the investigator at day 180	180 days
Adverse events	180 days

Collaborators and Investigators

• Sponsor: SunWave Pharma
• Collaborators: Opera CRO, a TIGERMED Group Company
• Investigators: Principal Investigator: Calin Giurcaneanu, MD, Spitalul Universitar de Urgenta Elias, Sectia Dermatologie

Publications and helpful links

General Publications

• Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation. 2005 May 10;111(18):2398-409. doi: 10.1161/01.CIR.0000164199.72440.08. No abstract available.
• Sezer A, Usta U, Kocak Z, Yagci MA. The effect of a flavonoid fractions diosmin + hesperidin on radiation-induced acute proctitis in a rat model. J Cancer Res Ther. 2011 Apr-Jun;7(2):152-6. doi: 10.4103/0973-1482.82927.
• Perrin M, Ramelet AA. Pharmacological treatment of primary chronic venous disease: rationale, results and unanswered questions. Eur J Vasc Endovasc Surg. 2011 Jan;41(1):117-25. doi: 10.1016/j.ejvs.2010.09.025. Epub 2010 Dec 3.
• Olin JW, Beusterien KM, Childs MB, Seavey C, McHugh L, Griffiths RI. Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study. Vasc Med. 1999;4(1):1-7. doi: 10.1177/1358836X9900400101.
• Porter JM, Moneta GL. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg. 1995 Apr;21(4):635-45. doi: 10.1016/s0741-5214(95)70195-8.
• Rabe E, Stucker M, Ottillinger B. Water displacement leg volumetry in clinical studies--a discussion of error sources. BMC Med Res Methodol. 2010 Jan 13;10:5. doi: 10.1186/1471-2288-10-5.
• Monograph. Diosmin. Altern Med Rev. 2004 Sep;9(3):308-11. No abstract available.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: October 6, 2016
• First Submitted That Met QC Criteria: October 6, 2016
• First Posted (Estimate): October 7, 2016

Study Record Updates

• Last Update Posted (Estimate): October 28, 2016
• Last Update Submitted That Met QC Criteria: October 27, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Venous Insufficiency
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Venous Insufficiency
• Other Study ID Numbers: OPSUN/0116/FS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes